The disorder known as Johne's disease was first described in 1895. Today, Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis), the causative agent of Johne's disease, is widely distributed both nationally and internationally in domestic ruminants such as cattle, sheep, goats, as well as wildlife such as rabbits, deer, antelopes, and bison. In 1996, the National Animal Health Monitoring System conducted a survey of dairy farms using serological analysis to determine the prevalence of Johne's disease in the U.S. The results of that study showed an estimated 20–40% of surveyed herds have some level of M. paratuberculosis. Furthermore, it is estimated that annual losses in the U.S. from M. paratuberculosis in cattle herds may exceed $220 million.
The pathogenesis of M. paratuberculosis has been recently reviewed by Harris and Barletta (2001, Clin. Microbiol. Rev., 14:489–512). Cattle become infected with M. paratuberculosis as calves but often do not develop clinical signs until 2 to 5 years of age. The primary route of infection is through ingestion of fecal material, milk or colostrum containing M. paratuberculosis microorganisms. M cells likely serve as the port of entry for M. paratuberculosis into the lymphatic system similar to other intracellular pathogens such as salmonella. M. paratuberculosis survive and may even replicate within macrophages in the wall of the intestine and in regional lymph nodes. After an incubation period of several years, extensive granulomatous inflammation occurs in the terminal small intestine, which leads to malabsorption and protein-losing enteropathy. Cattle shed minimal amounts of M. paratuberculosis in their feces during the subclinical phase of infection, and yet over time, this shedding can lead to significant contamination of the environment and an insidious spread of infection throughout the herd before the animal is diagnosed. During the clinical phase of infection, fecal shedding of the pathogen is high and can exceed 1010 organisms/g of feces. The terminal clinical stage of disease is characterized by chronic diarrhea, rapid weight loss, diffuse edema, decreased milk production, and infertility. Although transmission of M. paratuberculosis occurs primarily through the fecal-oral route, it has also been isolated from reproductive organs of infected males and females.